Throughout this application various publications are referenced by numbers within parentheses. Full citations for theses publications may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
DNA-mediated gene transfer (DNA transfection) into NIH 3T3 murine fibroblast cells has been a fruitful means for detecting oncogenes in mammalian cellular DNA. The most extensively used transformation assay is the NIH 3T3 focus assay, in which transformed 3T3 cells are detected by their growth into dense foci (1). The focus assay has detected activated oncogenes in the genomes of many tumors and tumor-derived cell lines (2-6). The detected oncogenes are usually members of the ras gene family (5-11), although other genes have been characterized as well (5, 12-15). The alternative oncogene assay monitors tumor formation in immunodeficient mice following injection with transfected NIH 3T3 cells. The oncogenes met (16) and mas (17) were discovered by this method.
This invention discloses the use of a new transformation assay to detect a novel oncogene in DNA from human tumor-derived cell lines. The amino acid sequence encoded by the cDNA of this oncogene shows substantial homology to the previously characterized fibroblast growth factors, bFGF and aFGF (40,41), as well as to the amino acid sequence of two recently characterized oncogenes, int-2 and hst (42,43). For this reason applicants have designated this oncogene FGF-3 and continue this designation in the subject application. However, FGF-3 may alternatively be designated FGF-5 in future publications by the applicants.